Radiation InjuryBELLENCT02725840
Breast Cancer Lung Late Effects
An observational study of Radiation Injury and Breast Cancer, run by University of Florida at 2 sites in United States.
Trial summary
Through improved early detection and treatment, the number of long term breast cancer survivors continues to increase. There are now 2.8 million breast cancer survivors in the U.S. Florida alone adds over 9,000 women to the survivorship pool each year. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Radiation Injury, Breast Cancer
- What is being tested?
- Proton beam radiation therapy., X-ray based radiation therapy and Computed Tomography (CT) Scan
- Type of treatment
- Surgery or procedure
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2016to 14 Jan 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Breast cancer patients who are 18 years of age or older and have Stage II or higher disease and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall for the treatment of breast cancer will be enrolled in this study.
Who may be able to join
- Women who are at least 18 years of age.
- Women with Stage II or higher primary breast cancer and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall.
Who cannot join
- Patients not willing or able to submit to repeat chest CT scans and blood draws.
- Pregnant women.
- Patients who have previously had radiation treatment where any portion of the lung received greater than 5 Gy of radiation exposure.
- Women with bilateral breast cancer or metastatic disease to sites near the chest where additional radiation exposure to any portion of the lung of greater than 5 Gy is anticipated.
- Women with allergic reaction to all common CT contrast agents.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Radiation Oncology Davis Cancer Pavilion
Gainesville, Florida, 32611
University of Florida Health Proton Therapy Institute
Jacksonville, Florida, 32206
About this study
Official title: Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer
Through improved early detection and treatment, the number of long term breast cancer survivors continues to increase. There are now 2.8 million breast cancer survivors in the U.S. Florida alone adds over 9,000 women to the survivorship pool each year. Most receive radiation treatment (RT) of the affected breast and chest wall to reduce risk of recurrence. Even with advanced radiation techniques for dose conformality to minimize exposure of the highly sensitive lung, 14% of breast cancer patients treated with radiation develop clinical pulmonary toxicity, with 4% overall experiencing high grade clinical toxicity. Early diagnosis and intervention to mitigate lung radiation toxicity is increasingly important for the long term care of these survivors.
The investigators' goal is to better identify breast cancer patients at high risk for experiencing severe pulmonary toxicity requiring medical intervention, provide a means to identify toxicity early on, and tailor treatment and/or early intervention on a per-patient basis.
Read the detailed description
This project involves repeat chest computed tomography (CT) imaging and blood draws in subjects with breast cancer with radiation treatment to the affected breast and chest wall. The investigators are studying women receiving one of 2 types of radiation, either conventional X-rays (IMRT) or protons at the University of Florida Health Proton Therapy Institute (UFHPTI). These subjects typically would not receive follow-up chest CTs as per standard of care. All subjects will have received a pre-treatment chest CT scan as part of the treatment planning process. The investigators will enroll 30 subjects in the X-ray treatment group and 25 subjects in the proton group.
The investigative team has recently solved the technical challenges of extracting and characterizing lung vascular anatomy from clinical CT images of the chest and used these tools to characterize acute and chronic changes to pulmonary vascular structure in breast cancer patients receiving radiation to the chest wall for treatment of their cancer.
In Aim 1 of this study the investigators will compare lung vascular damage in women treated with conventional radiation with those treated at the UFHPTI. In Aim 2 they will use blood samples of the subjects of Aim 1 to investigate the differential role of inflammatory cytokines in the initiation and progression of pulmonary vascular radiation response in conventional versus proton radiation exposures. Aim 3 compares vascular damage with clinical pulmonary function assessment using spirometry and diffusion capacity of carbon monoxide (DLCO). Aim 4 ties together Aims 1-3 by employing and extending existing mathematical models of radiobiological response to improve and solidify the scientific understanding of the biological mechanisms of radiation response.
- Conditions
- Radiation Injury, Breast Cancer
- Being tested
- Proton beam radiation therapy., X-ray based radiation therapy, Computed Tomography (CT) Scan, Pulmonary Function Test (PFT)
- Keywords
- pulmonary vasculature, radiation late effects, proton therapy
- Medical subject headings
- Radiation Injuries, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proton beam radiation therapy.Radiation
Also called PTI
Proton bean radiation therapy interact differently with tissue with the result that protons are absorbed completely within the tissue instead of primarily passing through the entire body. The maximal depth of penetration is dependent upon the incoming velocity (energy) of the protons. Proton therapy utilizes this property to deliver radiation with very little dose beyond the targeted lesion. The dose-rate will be managed as part of the standard of care.
X-ray based radiation therapyRadiation
Also called conformal RT
The three-dimensional (3D) mapping of radiation dose distributions permits detailed assessment of local vascular damage as a function of treatment factors of dose, dose-rate. The dose-rate will be managed as part of the standard of care.
Computed Tomography (CT) ScanProcedure or surgery
Computed Tomography (CT) Scan of the chest will be performed at 1, 3, 6, 12, 18 and 24 months
Pulmonary Function Test (PFT)Procedure or surgery
Pulmonary function test (PFT) will be performed at pre-treatment, and at 6 and 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Proton beam radiation therapy | The participants in this group will be receiving proton therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT). Receives: Radiation: Proton beam radiation therapy.; Procedure: Computed Tomography (CT) Scan; Procedure: Pulmonary Function Test (PFT) | |
| X-ray based radiation therapy | The participants in this group will be receiving X-ray radiation therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT). Receives: Radiation: X-ray based radiation therapy; Procedure: Computed Tomography (CT) Scan; Procedure: Pulmonary Function Test (PFT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The lower dose limit for measurable change in number of small blood vessels as characterized from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
The investigators seek to identify differences between the treatment modalities (proton versus X-ray) in regards to the lower dose limits for change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique.
Measured: 2 years
Vessel number change dose-response relationship as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
Identify change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, as a function of radiation dose exposure across the lung.
Measured: 2 years
Recovery of number of small blood vessels as measured from chest CT scans acquired at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
Identify differences in temporal patterns of vessel regeneration following radiation exposure as a function of dose and of modality (proton versus X-ray).
Measured: 2 years
Temporal patterns of blood cytokines following radiation exposure as measured from blood draws a pre-treatment and at 1,3,6, 12 and 24 months (= 2 years), and compared between proton versus X-ray radiation therapy.
Quantify differences in temporal patterns of levels of cytokines in the blood in breast cancer patients receiving conventional X-ray versus proton RT using serial blood draws that are time-matched with the CT chest scans.
Measured: 2 years
Correlate change in number of small blood vessels as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) with clinical pulmonary function test outcomes at 6 and 12 months.
Correlate change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, with clinical pulmonary function test (spirometry and diffusion capacity for carbon monoxide) outcomes to identify potential predictive value of early vascular changes to conventional clinical measures of late effects.
Measured: 1 year
Secondary outcomes (2)
Compare incidence of long-term clinical grade 2 and higher radiation toxicity to the lung as documented in patient medical records and compared between proton versus X-ray radiation therapy.
The goal is to monitor long-term (>8 year) incidence of clinical pulmonary toxicity in these subjects to identify any difference between X-ray and proton treatment methodologies.
Measured: 8 years
Compare duration of overall survival and whether death was attributed to lung radiation toxicity as documented in patient medical records and compared between proton versus X-ray radiation therapy.
The goal is to monitor long-term (>8 year) survival in these subjects to identify any difference between X-ray and proton treatment methodologies.
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2016 (estimated)
- Study startMay 2016
- Primary completion14 Jan 2022
- Study completion14 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Radiation InjuryStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Florida Department of Health
- Responsible party
- Sponsor
- Investigators
- Walter O'Dell, PhD, Principal investigator, University of FloridaJulie Bradley, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02725840
- Sponsor's protocol ID
- IRB201600387
- Other IDs
- OCR14962, 6BC09
- Acronym
- BELLE
- Status last verified
- Aug 2024
- First submitted
- 21 Mar 2016
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer
- ClinicalTrials.gov ID
- NCT02725840
- Acronym / sponsor ID
- BELLE / IRB201600387
- Conditions
- Radiation Injury, Breast Cancer
- Keywords
- pulmonary vasculature, radiation late effects, proton therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Florida Department of Health
- Study start
- May 2016 (actual)
- Primary completion
- 14 Jan 2022 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 1 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Through improved early detection and treatment, the number of long term breast cancer survivors continues to increase. There are now 2.8 million breast cancer survivors in the U.S. Florida alone adds over 9,000 women to the survivorship pool each year. Most receive radiation treatment (RT) of the affected breast and chest wall to reduce risk of recurrence. Even with advanced radiation techniques for dose conformality to minimize exposure of the highly sensitive lung, 14% of breast cancer patients treated with radiation develop clinical pulmonary toxicity, with 4% overall experiencing high grade clinical toxicity. Early diagnosis and intervention to mitigate lung radiation toxicity is increasingly important for the long term care of these survivors.
The investigators' goal is to better identify breast cancer patients at high risk for experiencing severe pulmonary toxicity requiring medical intervention, provide a means to identify toxicity early on, and tailor treatment and/or early intervention on a per-patient basis.
Detailed description
This project involves repeat chest computed tomography (CT) imaging and blood draws in subjects with breast cancer with radiation treatment to the affected breast and chest wall. The investigators are studying women receiving one of 2 types of radiation, either conventional X-rays (IMRT) or protons at the University of Florida Health Proton Therapy Institute (UFHPTI). These subjects typically would not receive follow-up chest CTs as per standard of care. All subjects will have received a pre-treatment chest CT scan as part of the treatment planning process. The investigators will enroll 30 subjects in the X-ray treatment group and 25 subjects in the proton group.
The investigative team has recently solved the technical challenges of extracting and characterizing lung vascular anatomy from clinical CT images of the chest and used these tools to characterize acute and chronic changes to pulmonary vascular structure in breast cancer patients receiving radiation to the chest wall for treatment of their cancer.
In Aim 1 of this study the investigators will compare lung vascular damage in women treated with conventional radiation with those treated at the UFHPTI. In Aim 2 they will use blood samples of the subjects of Aim 1 to investigate the differential role of inflammatory cytokines in the initiation and progression of pulmonary vascular radiation response in conventional versus proton radiation exposures. Aim 3 compares vascular damage with clinical pulmonary function assessment using spirometry and diffusion capacity of carbon monoxide (DLCO). Aim 4 ties together Aims 1-3 by employing and extending existing mathematical models of radiobiological response to improve and solidify the scientific understanding of the biological mechanisms of radiation response.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Proton beam radiation therapy | – | Radiation: Proton beam radiation therapy., Procedure: Computed Tomography (CT) Scan, Procedure: Pulmonary Function Test (PFT)The participants in this group will be receiving proton therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT). |
| X-ray based radiation therapy | – | Radiation: X-ray based radiation therapy, Procedure: Computed Tomography (CT) Scan, Procedure: Pulmonary Function Test (PFT)The participants in this group will be receiving X-ray radiation therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Breast cancer patients who are 18 years of age or older and have Stage II or higher disease and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall for the treatment of breast cancer will be enrolled in this study.
Key inclusion criteria (2 listed)
- Women who are at least 18 years of age.
- Women with Stage II or higher primary breast cancer and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall.
Key exclusion criteria (5 listed)
- Patients not willing or able to submit to repeat chest CT scans and blood draws.
- Pregnant women.
- Patients who have previously had radiation treatment where any portion of the lung received greater than 5 Gy of radiation exposure.
- Women with bilateral breast cancer or metastatic disease to sites near the chest where additional radiation exposure to any portion of the lung of greater than 5 Gy is anticipated.
- Women with allergic reaction to all common CT contrast agents.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proton beam radiation therapy.Also: PTIProton bean radiation therapy interact differently with tissue with the result that protons are absorbed completely within the tissue instead of primarily passing through the entire body. The maximal depth of penetration is dependent upon the incoming velocity (energy) of the protons. Proton therapy utilizes this property to deliver radiation with very little dose beyond the targeted lesion. The dose-rate will be managed as part of the standard of care. | Radiation | Proton beam radiation therapy |
| X-ray based radiation therapyAlso: conformal RTThe three-dimensional (3D) mapping of radiation dose distributions permits detailed assessment of local vascular damage as a function of treatment factors of dose, dose-rate. The dose-rate will be managed as part of the standard of care. | Radiation | X-ray based radiation therapy |
| Computed Tomography (CT) ScanComputed Tomography (CT) Scan of the chest will be performed at 1, 3, 6, 12, 18 and 24 months | Procedure or surgery | Proton beam radiation therapy, X-ray based radiation therapy |
| Pulmonary Function Test (PFT)Pulmonary function test (PFT) will be performed at pre-treatment, and at 6 and 12 months. | Procedure or surgery | Proton beam radiation therapy, X-ray based radiation therapy |
Primary outcome
The lower dose limit for measurable change in number of small blood vessels as characterized from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
Time frame: 2 years
The investigators seek to identify differences between the treatment modalities (proton versus X-ray) in regards to the lower dose limits for change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique.
Vessel number change dose-response relationship as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
Time frame: 2 years
Identify change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, as a function of radiation dose exposure across the lung.
Recovery of number of small blood vessels as measured from chest CT scans acquired at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy.
Time frame: 2 years
Identify differences in temporal patterns of vessel regeneration following radiation exposure as a function of dose and of modality (proton versus X-ray).
Temporal patterns of blood cytokines following radiation exposure as measured from blood draws a pre-treatment and at 1,3,6, 12 and 24 months (= 2 years), and compared between proton versus X-ray radiation therapy.
Time frame: 2 years
Quantify differences in temporal patterns of levels of cytokines in the blood in breast cancer patients receiving conventional X-ray versus proton RT using serial blood draws that are time-matched with the CT chest scans.
Correlate change in number of small blood vessels as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) with clinical pulmonary function test outcomes at 6 and 12 months.
Time frame: 1 year
Correlate change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, with clinical pulmonary function test (spirometry and diffusion capacity for carbon monoxide) outcomes to identify potential predictive value of early vascular changes to conventional clinical measures of late effects.
2 secondary outcomes
Compare incidence of long-term clinical grade 2 and higher radiation toxicity to the lung as documented in patient medical records and compared between proton versus X-ray radiation therapy.
Time frame: 8 years
Compare duration of overall survival and whether death was attributed to lung radiation toxicity as documented in patient medical records and compared between proton versus X-ray radiation therapy.
Time frame: 8 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter O'Dell, PhD principal investigator
University of Florida
Julie Bradley, PhD principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Radiation Injury and Breast Cancer, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The lower dose limit for measurable change in number of small blood vessels as characterized from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy. (time frame: 2 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.